12-6317886-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001384598.1(PLEKHG6):c.1047C>T(p.His349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,555,870 control chromosomes in the GnomAD database, including 272,249 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (20362 hom., cov: 34)
  • Exomes 𝑓: 0.59 (251887 hom.)
• Consequence: PLEKHG6 NM_001384598.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

Genes affected

PLEKHG6 (HGNC:25562): (pleckstrin homology and RhoGEF domain containing G6) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in cell junction and centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHG6	NM_001384598.1	c.1047C>T	p.His349=	synonymous_variant	10/16	ENST00000684764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHG6	ENST00000684764.1	c.1047C>T	p.His349=	synonymous_variant	10/16		NM_001384598.1	P1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74850 AN: 152124 Hom.: 20367 Cov.: 34

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.475

GnomAD3 exomes AF: 0.519 AC: 84661 AN: 163106 Hom.: 23525 AF XY: 0.526 AC XY: 45247 AN XY: 85988

Gnomad AFR exome AF: 0.261

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.530

Gnomad EAS exome AF: 0.264

Gnomad SAS exome AF: 0.473

Gnomad FIN exome AF: 0.665

Gnomad NFE exome AF: 0.624

Gnomad OTH exome AF: 0.541

GnomAD4 exome AF: 0.592 AC: 830484 AN: 1403628 Hom.: 251887 Cov.: 48 AF XY: 0.590 AC XY: 408943 AN XY: 692606

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.663

Gnomad4 NFE exome AF: 0.627

Gnomad4 OTH exome AF: 0.550

GnomAD4 genome AF: 0.492 AC: 74841 AN: 152242 Hom.: 20362 Cov.: 34 AF XY: 0.492 AC XY: 36641 AN XY: 74434

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.477

Alfa AF: 0.583 Hom.: 41081

Bravo AF: 0.461

Asia WGS AF: 0.366 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	15
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: 13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1468603; hg19: chr12-6427052; COSMIC: COSV50603200; COSMIC: COSV50603200;